[关键词]
[摘要]
目的 基于网络药理学与分子对接技术探讨三七总皂苷治疗脓毒症的作用机制。方法 通过检索 TCMSP、Swiss Target Prediciton 和 PharmMapper 数据库得到三七总皂苷的作用靶点;在 Genecard、Drugbank、 Disgenet 和 OMIM 数据库检索脓毒症的疾病相关靶点;将筛选出的三七总皂苷作用靶点与脓毒症疾病相关靶点 取交集,作为三七总皂苷治疗脓毒症的潜在作用靶点。通过 STRING 数据库构建潜在作用靶点的蛋白互作 (PPI)网络,并筛选关键靶点;对潜在作用靶点进行 GO 功能及 KEGG 通路富集分析,构建药物-疾病-靶点-通 路网络;利用 AutoDock Vina 软件对三七总皂苷 5 种单体皂苷成分与三七总皂苷治疗脓毒症的关键靶点进行分 子对接验证。结果 获得三七总皂苷治疗脓毒症的潜在作用靶点 206 个;筛选得到 AKT1、TP53、SRC、 STAT3、JUN、TNF、IL6、MAPK1、PIK3R1 和 IL1B 等关键靶点。潜在作用靶点 GO 功能富集分析得到 2 548 项 生物过程(BP)条目,174 项分子功能(MF)条目,47 项细胞组分(CC)条目;KEGG 通路富集分析共得到 171 条 信号通路。三七总皂苷主要活性成分三七皂苷 R1 、人参皂苷 Rg1、人参皂苷 Re、人参皂苷 Rb1、人参皂苷 Rd 与关键靶点 AKT1、TP53、STAT3、SRC、JUN 具有较强的结合活性。结论 三七总皂苷可能通过 AKT1、 TP53、SRC、STAT3、TNF 等关键靶点,作用于 PI3K-Akt、AGE-RAGE 等主要信号通路,进而影响脓毒症的 炎症反应、细胞凋亡和凝血反应等生理过程,发挥治疗脓毒症的作用。
[Key word]
[Abstract]
Objective To explore the mechanism of Panax notoginsenosides in the treatment of sepsis based on network pharmacology and molecular docking technology. Methods The action targets of total saponins of Panax notoginsenosides were obtained by searching the databases of TCMSP,Swiss Target Prediciton and PharmMapper, and the disease-related targets of sepsis were searched in the databases of Genecard, Drugbank, Disgenet and OMIM. The selected targets of total saponins of Panax notoginsenosides were intersected with the disease-related targets of sepsis,which were used as potential targets for the treatment of sepsis. The protein-protein interaction (PPI) network of potential targets was constructed by STRING database,and the key targets were screened;the potential targets were analyzed by GO function and KEGG pathway enrichment analysis, and the drug-disease-target-pathway network was constructed;the molecular docking of five monomer saponins of Panax notoginsenosides and the key targets of Panax notoginsenosides in the treatment of sepsis was studied by AutoDock Vina software. Results A total of 206 potential targets of Panax notoginsenosides in the treatment of sepsis were obtained,and key targets such as AKT1,TP53,SRC,STAT3,JUN,TNF,IL6,MAPK1,PIK3R1 and IL1B were screened. A total of 2 548 biological process (BP) items,174 molecular function (MF) items and 47 cellular component (CC) items were obtained by GO functional enrichment analysis of potential targets, and 171 signal pathways were obtained by KEGG pathway enrichment analysis. The main active components of Panax notoginsenosides R1, ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1 and ginsenoside Rd have strong binding activity with key targets AKT1,TP53,STAT3,SRC and JUN. Conclusion Panax notoginsenosides may act on the main signal pathways such as PI3K-Akt and AGE-RAGE through the key targets such as AKT1,TP53,SRC,STAT3 and TNF,and then affect the physiological processes such as inflammation,apoptosis and blood coagulation in sepsis,and play a role in the treatment of sepsis.
[中图分类号]
R285.5;R857.3
[基金项目]
广东省中医药管理局科研项目(20221189)